Financial support and protected time is requested to support a career development program comprised of mentored clinical research and formal course work leading to a Masters in Clinical Research from a Graduate Training Program in Translational Investigation (K30). The long-term career objective of this grant application is to become a successful, independent clinical investigator in urological oncology focussing on patient-oriented research, ultimately leading to a tenured faculty position. The proposed research project will serve as a tool from which to gain mentored research experience. The overall goal of the proposed research is to combine the extensive clinical and experimental resources in kidney cancer at UCLA School of Medicine to identify the genetic and molecular signature of response to immunotherapy for patients with metastatic renal cell carcinoma (RCC). Although some aspects of the molecular genetics of RCC have begun to be appreciated, little is known about the genes and proteins underlying its unpredictable clinical course and whether or not an individual patient will or will not respond to immunotherapy. The resources at UCLA provide a unique opportunity to take advantage of new genome wide discovery tools (e.g., expression arrays, genomic databases) which will provide new strategies to tackle tumor classification and tumor biology. The combination of a strong clinical database, mRNA expression array studies from fresh tumor samples, comparative genomics and gene sequencing, and large archived tissue sample resources organized in a tissue array format may provide new tools to uncover novel aspects of RCC biology. I propose to use chromosomal analysis (aim 1), VHL mutation analysis (aim 2), as well as molecular profiling of global gene expression patterns (aim 3) to identify genetic and molecular markers for kidney cancer progression, metastasis, and response to immunotherapy. Lastly, human tissue arrays and an extensive clinical database will be used to externally validate the experimental markers (aim 4). Ultimately, this proposal is a platform from which I seek training to further a career in cancer research at the clinical/translational interface of oncologic care with a special interest in gene and immune-based therapies for renal cell carcinoma.